Comparison of obinutuzumab and rituximab for treating primary membranous nephropathy.

Introduction: This study compared the effectiveness and safety profiles of obinutuzumab and rituximab in the treatment of patients with primary membranous nephropathy.

Methods: Patients with primary membranous nephropathy who had urine protein ≥ 3.5 g/24 hours and estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 despite six months of angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker and treatment with obinutuzumab or rituximab were included and matched by propensity score (ratio: 1:2) based on age, sex, urine protein, eGFR, and titers of Anti-Phospholipase A2 receptor (PLA2R) antibody. The primary outcome was defined as a combination of partial or complete remission at 12 months. Logistic regression models, Kaplan Meier curves, and absolute risk differences were employed to compare the therapeutic effectiveness and safety profiles of obinutuzumab and rituximab.

Results: Sixty-three patients with primary membranous nephropathy were included in the study, with 21 patients receiving obinutuzumab and 42 patients receiving rituximab. At 12 months, the primary outcome was achieved in 20 of 21 patients in the obinutuzumab group and 28 of 42 patients in the rituximab group (obinutuzumab vs. rituximab: 95% vs. 67%; odds ratio (OR): 10.00, 95% confidence intervals (CI):1.21-82.35, P=0.03). Moreover, patients in the obinutuzumab group acquired more complete remission (obinutuzumab vs. rituximab: 38% vs. 14%; OR: 3.69, 95% CI:1.08-12.68, P=0.04). In PLA2R-associated primary membranous nephropathy subgroup analyses, patients in obinutuzumab group sustained lower CD19 B cell counts (CD19 B cell counts: median (IQR) 0 (0-6) cells/ul vs. 20 (3-58) cells/ul, P=0.002) and were more prone to achieve immunological remission (defined as PLA2R antibody <2 RU/ml) at six months [obinutuzumab vs. rituximab: 92% (12 out of 13) vs. 64% (16 out of 25), P=0.06] than rituximab. Both treatment regimens were well tolerated.

Conclusions: Our study demonstrated that obinutuzumab is associated with higher odds of clinical remission compared to rituximab at 12 months which may be due to higher immunological remission at six months with a similar safety profile in patients with primary membranous nephropathy.